چکیده انگلیسی

Impulsivity, inattention and poor behavioral inhibition are common deficits in pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD). This study aimed to identify similarities and differences in the neural substrate of response inhibition deficits that are associated with these disorders. A functional magnetic resonance imaging (fMRI) study was conducted on 15 unmedicated PBD patients (Type I, manic/mixed), 11 unmedicated ADHD patients, and 15 healthy controls (HC) (mean age = 13.5 years; S.D. = 3.5). A response inhibition task examined the ability to inhibit a motor response to a target when a stop cue appeared shortly after. The PBD and ADHD groups did not differ on behavioral performance, although both groups were less accurate than the HC group. fMRI findings showed that for trials requiring response inhibition, the ADHD group, relative to the PBD and HC groups, demonstrated reduced activation in both ventrolateral (VLPFC) and dorsolateral (DLPFC) prefrontal cortex, and increased bilateral caudate activation compared with HC. The PBD group, relative to HC, showed decreased activation in the left VLPFC, at the junction of the inferior and middle frontal gyri, and in the right anterior cingulate cortex (ACC). Prefrontal dysfunction was observed in both the ADHD and PBD groups relative to HC, although it was more extensive and accompanied by subcortical overactivity in ADHD.

مقدمه انگلیسی

Pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD) have distinct as well as overlapping clinical symptoms. PBD is characterized by emotional dysregulation, elated mood, irritability, increased energy and disinhibition (Geller et al., 1998, Pavuluri et al., 2007 and Pavuluri and Passarotti, 2008). ADHD is characterized by motor hyperactivity, inattention, impulsivity and poor behavioral control (American Psychiatric Association, 1994 and Barkley, 1997).
Neuropsychological studies often report similar neurocognitive deficits in patients with ADHD and PBD. Patients with PBD have deficits in cognitive flexibility, sustained attention and verbal working memory, independent of illness status (Dickstein et al., 2005 and Pavuluri et al., 2006). Similarly, ADHD patients exhibit deficits in executive functions, attention, vigilance, working memory, planning and response inhibition (Doyle et al., 2005, Rubia et al., 2001 and Seidman et al., 2004). Moreover, recent studies also suggest that adolescents with ADHD may present more severe neurocognitive impairment than those with PBD, with or without a comorbid ADHD diagnosis (Rucklidge, 2006 and Galanter and Leibenluft, 2008). Given overlapping clinical symptoms, neurocognitive impairment, and the high levels of comorbid ADHD in patients with PBD (Geller et al., 1998 and Biederman et al., 2000), there is a need for improved understanding of the similar and distinct neural substrates of these two developmental disorders.
Studies of adolescents with ADHD (Casey et al., 1997 and Rubia et al., 1999) implicate the dorsolateral prefrontal cortex (DLPFC), the ventrolateral prefrontal cortex (VLPFC), and the dorsal striatum as regions of dysfunction in this disorder. For instance, recent functional magnetic resonance imaging (fMRI) that examined selective attention using the Flanker Task (Vaidya et al., 1998) and response inhibition using a Go-NogoTask (Casey et al., 1997, Durston et al., 2003, Durston et al., 2006 and Tamm et al., 2004) or a Stop-Signal Task (Plitzka et al., 2006 and Rubia et al., 1999) in adolescents with ADHD found decreased activation in prefrontal regions such as the VLPFC, the anterior cingulate cortex (ACC), and the mesial prefrontal cortex, as well as the caudate (Rubia et al., 1999). In addition to dysfunction of ventral fronto-striatal circuits, Durston et al. (2003) also found increased recruitment of posterior temporal and parietal regions in children with ADHD as compared with age-matched healthy controls (HC) during a Go-Nogo task, which has been considered a compensatory phenomenon for prefrontal cortex (PFC) underactivity (Durston et al., 2003;Vaidya et al., 2005). Findings of functional fronto-striatal abnormalities are also in line with studies showing reduced tissue volumes in the DLPFC and caudate in pediatric populations with ADHD (Castellanos et al., 1994, Castellanos et al., 1996, Castellanos et al., 2002, Filipek et al., 1997 and Seidman et al., 2006).
With regard to PBD, a recent study using the Stop-Signal Task (Leibenluft et al., 2007) found that during failed Stop trials children with PBD, regardless of comorbid ADHD or medication, showed decreased activation in the right VLPFC and bilateral striatum when compared with HC. Similarly, decreased VLPFC activation in children with PBD compared with HC was found by Pavuluri et al. (2008) during an emotional Stroop Task. In another study that employed a color-naming Stroop Task (Blumberg et al., 2003a), patients with PBD exhibited increased activation in putamen and thalamus compared with HC. Moreover, a growing number of studies are reporting dysfunction in rostral ACC, a region important for emotion regulation, in PBD (Pavuluri et al., 2006 and Malhi et al., 2005; for a review, see Fountoulakis et al., 2008).
To delineate disorder-specific disturbances in functional brain systems that might account for behavioral control deficits (e.g., impulsivity, motor disinhibition) associated with both disorders, we contrasted brain activation in pediatric patients with PBD and with ADHD to that of HC using a Response Inhibition Task.
The main goal of the present study was to examine the neural underpinnings of motor inhibition as compared with motor response in patients with ADHD and PBD, rather than addressing the more specific case of response inhibition in the context of a pre-potent tendency to respond, as in a typical Stop-Signal Task (Logan et al., 1984), because we think it is important to first elucidate the basic circuits for motor inhibition versus motor execution in these patients. Therefore, the present experimental task examined the ability to execute a motor response to a target, or inhibit a motor response that is already on the way, when a stop cue appears shortly after the target. Our primary fMRI comparison was between blocks of trials requiring predominantly inhibition of a motor response already on the way, and blocks of trials that required predominantly a motor response.
We hypothesized that both the PBD and ADHD groups would show impairment in response inhibition compared with the HC group. Moreover, we predicted that compared with findings in healthy controls, the PFC and the fronto-striatal stream would be more affected in ADHD (Casey et al., 1997, Bush et al., 1999 and Rubia et al., 1999), whereas the PBD group would exhibit more localized dysfunction in regulatory regions such as the VLPFC and pregenual ACC (Pavuluri and Passarotti, 2008 and Pavuluri et al., 2008).

نتیجه گیری انگلیسی

While behavioral deficits in response inhibition and attention are common to both PBD and ADHD, the present study revealed a more generalized profile of prefrontal dysfunction in ADHD patients compared to PBD patients during a Response Inhibition Task. While in ADHD response inhibition deficits may be driven by a more extensive dysfunction of PFC and motor control systems, in PBD they may be driven by more localized dysfunction of regulatory VLPFC and ACC regions.